Post-Translational Modifications of cGAS-STING: A Critical Switch for Immune Regulation

Cells. 2022 Sep 28;11(19):3043. doi: 10.3390/cells11193043.

Abstract

Innate immune mechanisms initiate immune responses via pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of the PRRs, senses diverse pathogenic or endogenous DNA and activates innate immune signaling pathways, including the expression of stimulator of interferon genes (STING), type I interferon, and other inflammatory cytokines, which, in turn, instructs the adaptive immune response development. This groundbreaking discovery has rapidly advanced research on host defense, cancer biology, and autoimmune disorders. Since cGAS/STING has enormous potential in eliciting an innate immune response, understanding its functional regulation is critical. As the most widespread and efficient regulatory mode of the cGAS-STING pathway, post-translational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are generally considered a regulatory mechanism for protein destruction or renewal. In this review, we discuss cGAS-STING signaling transduction and its mechanism in related diseases and focus on the current different regulatory modalities of PTMs in the control of the cGAS-STING-triggered innate immune and inflammatory responses.

Keywords: cGAS-STING; dsDNA sensing; innate immunity; post-translational modification; type I interferons.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Cytokines / metabolism
  • DNA / metabolism
  • Interferon Type I* / metabolism
  • Membrane Proteins* / metabolism
  • Nucleotidyltransferases / metabolism
  • Protein Processing, Post-Translational

Substances

  • Amino Acids
  • Cytokines
  • Interferon Type I
  • Membrane Proteins
  • DNA
  • Nucleotidyltransferases

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant numbers 82174222) and the Natural Science Foundation of Shandong Province (grant number ZR2021LZY015) to C.S.